The ferric uptake regulator represses type VI secretion system function by binding directly to the clpV promoter in Salmonella enterica serovar Typhimurium
The ferric uptake regulator represses type VI secretion system function by binding directly to the clpV promoter in Salmonella enterica serovar Typhimurium
复制标题
铁摄取调节剂通过直接与鼠伤寒沙门氏菌中的 clpV 启动子结合来抑制 VI 型分泌系统功能
DOI：
10.1128/iai.00562-19
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发表时间：
2019
影响因子：
3.1
通讯作者：
Shengqing Yu
中科院分区：
文献类型：
--
作者：
Shaohui Wang;Denghui Yang;Xiaojun Wu;Zhengfei Yi;Yang Wang;Suhua Xin;Dong Wang;Mingxing Tian;Tao Li;Jingjing Qi;Chan Ding;Shengqing Yu
VI型分泌系统（T6 SS）是高度保守和复杂的蛋白质分泌系统，其将效应蛋白递送到真核宿主或其他细菌中。T6 SSs受到多种调控系统的精确调控，使细菌能够适应不同的环境。沙门氏菌致病性岛6（SPI-6）内的T6 SS在感染过程中被激活，它有助于肠道沙门氏菌鼠伤寒血清型（S.Typhimurium）的发病机制以及细菌间的竞争。然而，SPI-6 T6 SS在鼠伤寒沙门氏菌中的调节还不清楚。在这项研究中，我们发现SPI-6 T6 SS核心基因lpV在响应铁耗尽条件和感染期间显著上调。铁吸收调节剂（Fur）在铁营养培养基中抑制lpV的表达。此外，电泳迁移率变化和DNA酶I足迹分析显示，Fur直接结合到lpV启动子区域的多个位点，跨越转录起始位点。我们还观察到Fur介导的对clpV抑制的解除有助于Typhimurium的细菌间竞争活性和致病性。这些发现为Fur对鼠伤寒沙门氏菌SPI-6 T6 SS表达和功能活性的直接调控提供了新的思路，从而有助于阐明细菌适应性和毒力的机制。
Type VI secretion systems (T6SSs) are highly conserved and complex protein secretion systems that deliver effector proteins into eukaryotic hosts or other bacteria. T6SSs are regulated precisely by a variety of regulatory systems, which enables bacteria to adapt to varied environments. A T6SS withinSalmonellapathogenicity island 6 (SPI-6) is activated during infection, and it contributes to the pathogenesis, as well as interbacterial competition, of Salmonella enterica serovar Typhimurium (S.Typhimurium). However, the regulation of the SPI-6 T6SS inS.Typhimurium is not well understood. In this study, we found that the SPI-6 T6SS core geneclpVwas significantly upregulated in response to the iron-depleted condition and during infection. The global ferric uptake regulator (Fur) was shown to repress theclpVexpression in the iron-replete medium. Moreover, electrophoretic mobility shift and DNase I footprinting assays revealed that Fur binds directly to theclpVpromoter region at multiple sites spanning the transcriptional start site. We also observed that the relieving of Fur-mediated repression onclpVcontributed to the interbacterial competition activity and pathogenicity ofS.Typhimurium. These findings provide insights into the direct regulation of Fur in the expression and functional activity of SPI-6 T6SS inS.Typhimurium and thus help to elucidate the mechanisms of bacterial adaptability and virulence.